tbuckley/cabot-search huggingface dataset:
Outcomes of a resilient living program for patients with advanced cancer and their caregivers.
Authors: Deirdre R. Pachman, Sherry Chesak, Susanne M Cutshall, Jayawant Mandrekar, Teresa A Rummans, Matthew M Clark, Maria I Lapid
Journal: Journal of Clinical Oncology (2022)

e24087 Background: Patients with advanced cancer and their caregivers experience a substantial amount of distress. Limited research suggests that mindfulness-based interventions may improve quality of life and reduce anxiety. The virtually delivered Resilient Living program consisted of online modules, a print journal, and a total of 4 virtual training sessions focused on techniques for managing stress and building resilience (mindful presence, uplifting emotions, reframing experiences through principles of gratitude, compassion, acceptance, meaning, and forgiveness). The current pilot study was performed to assess the feasibility of the virtual Resilient Living Program for patients with advanced cancer and their caregivers, as well as preliminary effects on anxiety and related outcomes. Methods: Eligible patients included those age ≥18 years with a diagnosis of advanced cancer with expected prognosis &gt; 6 months. Feasibility was defined as consent of at least 25% of eligible patients and their caregivers. Adherence was defined as 75% of the enrolled participants completing at least 3 of the 4 Resilient Living sessions. The primary outcome measure was anxiety as measured by the GAD-7; others included stress (PSS), quality of life (LASA), sleep (ISI), resiliency (Resiliency Scale), and fatigue (PROMIS-Fatigue SF). Results: Seventy-two eligible patients were referred to the study, of these 33 patients enrolled (46% enrollment), 15 also had a caregiver enroll. Thirty participants completed at least 3 virtual sessions (63% adherence). Data was collected at baseline, week 5 (after 2 session), week 9 (after 4 sessions), and week 12 (1 month after completion) for patients and caregivers. There were statistically significant improvements in anxiety at weeks 5, 9 and 12 (i.e., p &lt; 0.05). Other results are outlined in the table. Conclusions: Virtual participation in the Resilient Living Program is feasible and acceptable for patients with advanced cancer and their caregivers. Data from this pilot study suggest that the program may positivity impact anxiety, stress, sleep, quality of life and resiliency. A larger randomized prospective clinical trial is warranted to confirm these preliminary findings. Clinical trial information: NCT04480008. [Table: see text]
Post-biopsy cell-free DNA from blood in primary prostate cancer: How to get genetics data for decision making
Authors: M. Lazzeri, G. Chiarelli, M. Corbetta, R. Asselta, I. De Simone, G. Soldà, S. Duga, M. Zuradelli, P. Casale, A. Saita, G. Lughezzani, G. Guazzoni, R. Hurle, A. Benetti, C. Saitta, V. Fasulo, N. Buffi
Journal: European Urology (2022)
A robust artificial intelligence approach for histopathological evaluation of prostate biopsies
Authors: N. Mulliqi, K. Kartasalo, X. Ji, K. Szolnoky, H. Olsson, A. Blilie, M. Braun, M. Gambacorta, K. Hotakainen, E.A.M. Janssen, S.R. Kjosavik, R. Łowicki, B.G. Pedersen, K.D. Sørensen, B.P. Ulhøi, P. Ruusuvuori, L. Egevad, M. Eklund
Journal: European Urology (2022)
High Levels of Circulating Tumor Plasma Cells as a Key Hallmark of Aggressive Disease in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma
Authors: Luca Bertamini, Stefania Oliva, Delia Rota-Scalabrini, Laura Paris, Sonia Morè, Paolo Corradini, Antonio Ledda, Massimo Gentile, Giovanni De Sabbata, Giuseppe Pietrantuono, Anna Pascarella, Patrizia Tosi, Paola Curci, Milena Gilestro, Andrea Capra, Piero Galieni, Francesco Pisani, Ombretta Annibali, Federico Monaco, Anna Marina Liberati, Salvatore Palmieri, Mario Luppi, Renato Zambello, Francesca Fazio, Angelo Belotti, Paola Tacchetti, Pellegrino Musto, Mario Boccadoro, Francesca Gay
Journal: Journal of Clinical Oncology (2022)

High levels of circulating tumor plasma cells (CTC-high) in patients with multiple myeloma are a marker of aggressive disease. We aimed to confirm the prognostic impact and identify a possible cutoff value of CTC-high for the prediction of progression-free survival (PFS) and overall survival (OS), in the context of concomitant risk features and minimal residual disease (MRD) achievement.CTC were analyzed at diagnosis with two-tube single-platform flow cytometry (sensitivity 4 × 10-5) in patients enrolled in the multicenter randomized FORTE clinical trial (ClinicalTrials.gov identifier: NCT02203643). MRD was assessed by second-generation multiparameter flow cytometry (sensitivity 10-5). We tested different cutoff values in series of multivariate (MV) Cox proportional hazards regression analyses on PFS outcome and selected the value that maximized the Harrell's C-statistic. We analyzed the impact of CTC on PFS and OS in a MV analysis including baseline features and MRD negativity.CTC analysis was performed in 401 patients; the median follow-up was 50 months (interquartile range, 45-54 months). There was a modest correlation between the percentage of CTC and bone marrow plasma cells (r = 0.38). We identified an optimal CTC cutoff of 0.07% (approximately 5 cells/µL, C-index 0.64). In MV analysis, CTC-high versus CTC-low patients had significantly shorter PFS (hazard ratio, 2.61; 95% CI, 1.49 to 2.97, P < .001; 4-year PFS 38% v 69%) and OS (hazard ratio, 2.61; 95% CI, 1.49 to 4.56; P < .001; 4-year OS 68% v 92%). The CTC levels, but not the bone marrow plasma cell levels, affected the outcome. The only factor that reduced the negative impact of CTC-high was the achievement of MRD negativity (interaction P = .039).In multiple myeloma, increasing levels of CTC above an optimal cutoff represent an easy-to-assess, robust, and independent high-risk factor. The achievement of MRD negativity is the most important factor that modulates their negative prognostic impact.
Contemporary management of pain in cirrhosis: Toward precision therapy for pain
Authors: Alexis Holman, Neehar Parikh, Dan J. Clauw, David A. Williams, Elliot B. Tapper
Journal: Hepatology (2022)

Chronic pain is highly prevalent in patients with cirrhosis and is associated with poor health-related quality of life and poor functional status. However, there is limited guidance on appropriate pain management in this population, and pharmacologic treatment can be harmful, leading to adverse outcomes, such as gastrointestinal bleeding, renal injury, falls, and hepatic encephalopathy. Chronic pain can be categorized mechanistically into three pain types: nociceptive, neuropathic, and nociplastic, each responsive to different therapies. By discussing the identification, etiology, and treatment of these three mechanistic pain descriptors with a focus on specific challenges in patients with cirrhosis, we provide a framework for better tailoring treatments, including nonpharmacologic therapies, to patients' needs.
Perioperative complications after radical cystectomy for bladder cancer: An international multicenter collaboration
Authors: C. Lonati, L. Afferi, E. Di Trapani, S. Zamboni, C. Simeone, A. Briganti, F. Montorsi, G. Simone, F. Soria, C.M. Mir, R. Sanchez-Salas, M. Roumiguié, A. Antonelli, K. Hendricksen, A. Mattei, J. Teoh, S.F. Shariat, S. Albisinni, R. Hurle, A. Peroni, E. Xylinas, W. Krajewski, M. Rouprêt, M. Moschini
Journal: European Urology (2022)
Chemotherapy and radiofrequency hyperthermia in advanced ovarian cancer.
Authors: Gulhan Ipek Deniz, Ayten Can, Sualp Tansan
Journal: Journal of Clinical Oncology (2022)

e17550 Background: Ovarian cancer (OC) is the the leading cause of cancer death in females. Most cases present at advanced stage. Standard treatment is cytoreductive surgery before or after paclitaxel and carboplatin chemotherapy (CT) followed by maintenance treatment. Weekly CT is at least as effective as three weekly CT in OC, and may overcome resistance in some patients. Hyperthermia has been used alone or in combination with radiotherapy and chemotherapy in the treatment of advanced cancer. Radiofrequency hyperthermia (Oncothermia-OT) is theoretically more effective and comfortable form of hyperthermia due to its selective effects on tumor cells. Since most advanced patients have disease limited to the abdominal cavity, OT can be applied with a single electrode to cover the whole abdomen. Immediately following CT, OT may result in aggregation of DNA repair ezymes secreted in response to CT in cancer cells. Methods: We used weekly CT with paclitaxel or nab-paclitaxel with carboplatin followed immediately by OT. (Oncotherm-EHY 3010) to the whole abdomen for one hour for eighteen weeks in 22 consecutive patients with advanced (III or IV) ovarian/primary peritoneal cancer between 2016 and 2021. 19 patients received bevacizumab every three weeks in addition to chemotherapy.All pts had ECOG PS 0-1. Maintenance treatment was bevacizumab (19 patients) or olaparib (3 patients) for one year. Patients were followed by periodic CT/MRI/PET-CT and CA-125 levels. Results: All patients completed eighteen weeks of planned treatment. No unexpected or grade III-IV toxicity was observed. Complete response was obtained in 21 patients and partial response in one patient. Median follow up is 30 months (range 8-73 months).18 patients are alive, with 12 patients in ongoing remission and 6 patients receiving palliative treatment. 4 patients have died of cancer. Conclusions: Although this is a single center retrospective observation, the combination of weekly paclitaxel/nab-paclitaxel and carboplatin CT in combination with immediate weekly OT appears tolerable and feasible. Despite all of the limitations of this observation, activity of CT and OT appears promising. These findings should be confirmed with prospective randomized trials.
Propensity score-matched analysis comparing retrograde intrarenal surgery with percutaneous nephrolithotomy in anomalous kidneys
Authors: E.J. Lim, J.Y-C. Teoh, K.Y. Fong, E. Emiliani, N. Gadzhiev, D. Gorelov, Y. Tanidir, F. Sepulveda, A. Al-Terki, S. Khadgi, A. Mahajan, D. Ragoori, G. Ramalingam, V.C. Mohan, A.P. Ganpule, S. Kumar, D. Castellani, M. Monga, S. Cesare, F.C. Vicentini, O. Traxer, B.K. Somani, V. Gauhar
Journal: European Urology (2022)
Extended progression-free survival and long-term safety of nirogacestat in patients with desmoid tumors.
Authors: Geraldine Helen O'Sullivan Coyne, Shivaani Kummar, Seth M. Steinberg, Murielle Hogu, Naoko Takebe, Amisha Shah, James H. Doroshow, Alice P. Chen
Journal: Journal of Clinical Oncology (2022)

11545 Background: Desmoid tumors are rare, locally invasive, soft-tissue neoplasms that can cause significant morbidity and frequently recur despite surgery or radiation. The ongoing phase II trial of nirogacestat, a gamma-secretase inhibitor, in patients (pts) with recurrent, refractory desmoid tumors (NCT01981551), has reported disease stabilization and multiple partial responses as assessed by RECIST criteria (Kummar JCO 2017). Herein, we report long-term outcomes, tolerability, and safety of this study. Methods: A total of 17 pts enrolled in this open label, single arm, phase II study, completing accrual in 2014. Pts received 150 mg nirogacestat orally twice a day in continuous 3-week cycles. Objective treatment response was defined by RECIST 1.1 at cycle 1 and every 6 cycles thereafter using CT (affected area) per the primary study objective; optional MRI assessment was concurrently performed. Yearly CT scans of the chest, abdomen, and pelvis were performed on pts starting in 2016. Results: As of Dec. 31, 2021, 4/17 (23%) pts remain on nirogacestat treatment for over 7 years. The objective response rate has not changed since the 2017 publication [31.25% (5/16 evaluable patients), with an exact two-sided Clopper-Pearson 95% confidence interval of 11.0-58.7%], but the observed extended progression-free survival (PFS) is notable; no RECIST disease progression has been observed for any of the 16 evaluable patients at any point on study. Median time on treatment was 4.14 years (range: 0.17-7.99 years). Most common adverse events remain hypophosphatemia (13/17, 76%; 8 grade 3 [gr3], 5 gr2), diarrhea (13/17, 76%; 1 gr3, 4 gr2, 8 gr1), nausea (11/17, 65%; 11 gr1), AST increase (11/17, 65%; 1 gr2, 10 gr1), and lymphopenia (11/17, 65%; 2 gr2, 9 gr1); no pts required a dose reduction after the second year of therapy. Bone fractures (fx) were reported in 4 pts (3 female/1 male) during the first 4 years of treatment (1 hip fx, 1 rib fx, 2 metatarsal stress fxs). Two of these 4 pts experienced a further fx approximately 1 year later (contralateral metatarsal; hip). Both pts with hip fx were &gt; 10 years post-menopausal. Given median age at enrollment (34 years; range: 20-69 years) and reported fx events, bone health was evaluated with findings in keeping with expected range for age. No secondary malignancies have been identified to date. Conclusions: No patients receiving nirogacestat have progressed after a median of more than 4 years of treatment. The long duration of responses and lack of tumor progressions observed in this trial has informed the design of a phase III trial in pts with progressing desmoid tumors (NCT03785964) that is currently underway. Clinical trial information: NCT01981551.
Impact of circuit, interval-based exercise on insulin resistance and adiponectin among minority cancer survivors.
Authors: Cameron Christopher, Dong-Woo Kang, Amber Normann, Mary Norris, Christina Marie Dieli-Conwright
Journal: Journal of Clinical Oncology (2022)

12059 Background: Hispanic and Black adults have a heightened risk of metabolic syndrome compared to non-Hispanic white adults, increasing the risk of cardiovascular disease, diabetes, and co-morbid outcomes. Further, Hispanic and Black adults are more likely to be sedentary and obese than non-Hispanic white adults, leading to an increased risk of insulin resistance and poor metabolic health. Exercise improves cardiometabolic health, including insulin sensitivity and adiponectin, however few studies have focused on minority cancer survivors. The aim of our (NCT03284346) was to determine whether a 4-month circuit-based aerobic and resistance exercise intervention can improve insulin resistance and adiponectin levels in breast, prostate, and colorectal Hispanic and Black cancer survivors. Methods: Overweight or obese (BMI &gt; 25.0 kg/m2), sedentary breast, prostate or colorectal cancer survivors who self-identified as Hispanic or Black were randomized to exercise (n = 30) or usual care (n = 10). Survivors in the 4-month supervised exercise intervention participated in a thrice weekly, circuit, interval-based moderate-vigorous aerobic (65-85% of VO 2max ) and resistance (65-85% of 1-repetition maximum). Insulin resistance, assessed by Homeostasis Model of Assessment (HOMA-IR), and adiponectin levels were collected at baseline and post-intervention from fasting blood sample collection. Repeated-measures analysis of variance and t-tests were performed to assess within- and between-group differences. Results: The study sample was 66 ± 10.4 years old, Hispanic (55%), Black (45%), overweight (78%), and female (60%). Adherence to the intervention was 90% and post-intervention outcome measures were available on 100% of participants. Post-intervention, insulin resistance (within group mean difference: -3.2, p &lt; 0.01; between group mean difference: -4.5, p &lt; 0.01) and adiponectin levels (6.1 ug/mg, p &lt; 0.01; 8.6 ug/mg, p &lt; 0.01) significantly improved in the exercise group when compared to baseline and to usual care, respectively. Conclusions: A circuit, interval-based aerobic and resistance exercise intervention improved insulin resistance and adiponectin levels in breast, prostate, and colorectal minority cancer survivors. Accessible exercise interventions for minority cancer survivors may be effective to mitigate metabolic dysregulation and co-morbid conditions in survivorship and support cardiometabolic health. Clinical trial information: NCT03284346.
Blockers of Hyperpolarization-activated Cyclic Nucleotide-gated channels exhibit antimuscarinic properties in human atrial cardiomyocytes
Authors: M Gencarelli, A Laurino, V Balducci, V Spinelli, M Cameli, R Pecori, G Vistoli, R Matucci, E Cerbai, L Sartiani
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): M.I.U.R. PRIN 2017 to E.C and ECRF to L.S. Introduction Ivabradine (Iva), Zatebradine (Zat) and ZD7288 (ZD) are blockers of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels, which play definite electrophysiological functions in cardiac pacemakers, working cardiomyocytes, peripheral and central neurons [1]. Among them, Iva is in clinical use as bradycardic agent for uncontrolled angina and heart failure with reduced ejection fraction. Accumulating evidence suggests Iva may have a more complex pharmacological profile, including targets different from HCN channels [2, 3]. Reports on experimental atrial fibrillation, detrusor contraction and bladder overactivity [4] led us to hypothesize that muscarinic receptors (mAChRs) may represent still unexplored targets of Iva and analogues. Present study was designed to identify the effect of Iva on acetylcholine-gated inward-rectifier K+-current (IKACh), the main effector of atrial mAChRs, and to assess whether Iva and analogues interact directly with human atrial and recombinant mAChRs. Methods Patch-clamp recordings were performed on human atrial myocytes (hAMs) isolated from atrial appendages of patients in sinus rhythm. Competition and kinetic radioligand binding assays were performed on hAM preparations and on mAChR(1,2,3) expressed in heterologous systems. Results Patch-clamp recordings on hAMs demonstrated Iva is able to suppress IKAch similarly to atropine, thus suggesting a functional antagonism of Iva on atrial mAChRs. Competition binding assays on hAM membranes revealed Iva, Zat and ZD bind to mAChRs with affinity values close to those of muscarinic ligands carbachol (Cch) and gallamine (Gal). Competition binding assays on recombinant mAChR(1,2,3), which are functionally relevant in hAMs, showed all blockers are ligands for each single mAChR type with affinity values close to those of CCh and Gal. Finally, using dissociation binding assays on mAChR(2) lacking the allosteric binding site, we showed Iva and Zat behave as allosteric ligands with affinity values similar to Gal. Doking studies confirmed Iva and Zat, but not ZD, have the structural requirements necessary to interact with the allosteric and the orthosteric site of mAChR(2). Conclusions This study demonstrates Iva directly interacts with mAChR expressed in hAMs, showing antimuscarinic activity on IKAch. This property is likely dependent on a double interaction of Iva with the orthosteric and the allosteric site of mAChR(2). Zat, but not ZD, shows similar binding properties compared to Iva. Our results identify a novel pharmacological target for Iva and analogues in human atria, which may have important consequences for the function of the healthy and diseased atrium.
DIPG-25. Patterns of cerebrospinal fluid diversion and survival in children with diffuse intrinsic pontine glioma: a report from the International Diffuse Intrinsic Pontine Glioma Registry
Authors: Tabitha Cooney, Mariko DeWire-Schottmiller, Adam Lane, Raya Saab, Pratiti Bandopadhayay, Kathleen Dorris, Roger Packer, Lindsay Kilburn, Jane Minturn, Andrew Dodgshun, Sara Parkin, Stewart Goldman, Eric Sandler, Robert Greiner, Nicholas Gottardo, Hetal Dholaria, Scott Coven, Tim Hassall, Jordan Hansford, Yvan Samson, Sarah Leary, Ute Bartels, Adriana Fonseca, Eric Bouffet, Christopher Tinkle, Michelle Monje, Paul Fisher, David Ziegler, Murali Chintagumpala, Lars Wagner, Carl Koschmann, James Leach, Blaise Jones, Elisa Carrasquedo Benito, Hailey Bond, Brooklyn Chaney, Katie Black, Anthony Asher, Maryam Fouladi, Lindsey Hoffman, Katherine Warren
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: There are no standard practice guidelines for cerebrospinal (CSF) diversion for diffuse intrinsic pontine glioma (DIPG), nor clear understanding of potential for palliation and life-prolongation. We evaluated CSF diversion characteristics in children with DIPG to determine incidence, indications, symptom effects, and survival. METHODS: Data were extracted from subjects registered in the International DIPG registry (IDIPGR). Univariable analyses was performed using the Fisher’s exact test or Wilcoxon rank sum test. Survival was estimated using the Kaplan-Meier method. RESULTS: Evaluable patients (n=542) met criteria for DIPG diagnosis by central radiologic review; of those, 126 (23%) had permanent CSF diversion. Median time from diagnosis to diversion was 0.5 months (IQR 0.1-4.5 months). Those with permanent diversion were significantly younger (median 5.4 years vs 7.0 years, p&amp;lt;0.001) and had higher incidence of hydrocephalus at diagnosis (65.3% vs 11.9%, p&amp;lt;0.001). Permanent CSF diversion did not significantly impact overall survival (OS) (p=0.4), even amongst the 124 patients with hydrocephalus at presentation (p=0.20). Those with permanent diversion prior to radiation therapy demonstrated longer median OS than those in whom diversion was placed after radiation (14.3 vs 9.6 months, p=0.001). Patients reported significantly less headache and vomiting at last follow up after permanent CSF diversion compared to pre-diversion (p&amp;lt;0.0001 and p=0.001, respectively), however steroid use was also significantly higher at last follow-up after CSF diversion (p&amp;lt;0.001). CONCLUSIONS: Amongst an international cohort, DIPG patients who had permanent CSF diversion were significantly younger and had higher rates of hydrocephalus at initial presentation than those without permanent diversion. Symptoms of increased intracranial pressure improved in those with CSF diversion, although a direct effect may be confounded by increased steroid use. Permanent CSF diversion did not prolong overall survival in this large cohort of patients, even amongst those who presented with hydrocephalus.
Impact of surgical experience prior to robot-assisted partial nephrectomy on surgical outcomes: Large multicenter analysis with 2,500 patients
Authors: P. Zeuschner, S. Siemer, M. Stöckle, F. Schiefelbein, A. Schneller, G. Schön, C. Wiesinger, J. Pfuner, B. Ubrig, S. Gloger, D. Osmonov, A. Eraky, J. Witt, N. Liakos, C. Wagner, B. Hadaschik, J.P. Radtke, M. Al Nader, F. Imkamp, M. Kuczyk, S. Huusmann, N. Harke
Journal: European Urology (2022)